Methionine supplementation restores susceptibility to tigecycline by modifying epigenetic regulation and enhancing drug uptake.
Researchers found methionine can resensitize tigecycline-resistant E. coli and K. pneumoniae by promoting intracellular tigecycline accumulation and enhancing methylation modification of resistance genes.
The study involved researchers from several institutions engaged in microbiology and infectious disease research.
The findings were recently published, indicating recent research activity on the topic.
The study was conducted at various research facilities focused on infectious diseases.
The rise of multidrug-resistant bacteria necessitates innovative approaches to restore antibiotic efficacy, particularly for last-resort antibiotics like tigecycline.
The study implemented multi-omics analysis and both laboratory and animal model experiments to evaluate the effects of methionine on antibiotic resistance.
The study highlights the role of epigenetic modifications as well as metabolic pathways influencing bacterial responsiveness to antibiotics.
"Exogenous Met reprograms methionine metabolism and accelerates SAM converting to SAH, which activates 5mC methylation modification."
"To fully demonstrate Met-enabled Tig killing of tet(X4)-positive pathogens, we next assessed the in vivo efficacy of Tig plus Met."
"The combination of Met and Tig significantly reduced the loads of intracellular bacteria, indicating enhanced efficacy of the treatment."
The introduction will begin with the alarming rise of antibiotic-resistant bacteria and introduce tigecycline as the last-resort antibiotic affected by resistance genes. The discovery of methionine's role will also be addressed.
Background will entail explaining the rise of plasmid-mediated resistance, particularly the tet(X) gene family, and its impact on tigecycline's efficacy. The significance of finding alternative strategies to combat this issue will be highlighted.
The methodology and discovery should detail the approaches taken by researchers, including metabolomics and animal models to assess the impact of methionine. How methionine affects intracellular accumulation and gene expression will also be summarized.
Findings and their possible societal and scientific importance emphasizing methionine's role will be underlined, noting especially how it enhances drug efficacy against resistant strains. This will include findings about methylation modifications and another layer of metabolic reprogramming.
Finally, the conclusion will summarize how methionine supplementation can rejuvenate the effectiveness of tigecycline and the overall potential to utilize metabolic pathways and epigenetic modifications for overcoming antibiotic resistance, signaling the need for continued research.